Therapeutic agents that function as inhibitors of ASK1 signaling have the potential remedy or improve the lives of patients in need of treatment for diseases or conditions such as neurodegenerative, cardiovascular, inflammatory, autoimmune, and metabolic disorders. In particular, ASK1 inhibitors have the potential to treat cardio-renal diseases, including kidney disease, diabetic kidney disease, chronic kidney disease, fibrotic diseases (including lung and kidney fibrosis), respiratory diseases (including pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD) and acute lung injury), acute and chronic liver diseases. There is a need for improved or alternate processes to prepare compounds that are potent and exhibit improved pharmacokinetic and/or pharmacodynamic profiles for the treatment of diseases related to ASK1 activation.